ELK1

Chr X

ETS transcription factor ELK1

The protein is a transcription factor that binds purine-rich DNA sequences and forms ternary complexes with serum response factor to regulate immediate early gene transcription in response to MAPK signaling pathways. Mutations cause autosomal dominant neurodevelopmental disorder with developmental delay, intellectual disability, and behavioral abnormalities. The gene is highly constrained against loss-of-function variation (pLI 0.94, LOEUF 0.34), consistent with its essential role in cellular signaling and development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.34
Clinical SummaryELK1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
53 unique Pathogenic / Likely Pathogenic· 40 VUS of 131 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.937
Z-score 2.75
OE 0.00 (0.000.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.19Z-score
OE missense 0.55 (0.470.65)
104 obs / 188.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.34)
00.351.4
Missense OE0.55 (0.470.65)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 0 / 8.8Missense obs/exp: 104 / 188.6Syn Z: 0.66
DN
0.2997th %ile
GOF
0.3491th %ile
LOF
0.81top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.34

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

131 submitted variants in ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic1
VUS40
Likely Benign3
Benign1
52
Pathogenic
1
Likely Pathogenic
40
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
52
0
52
Likely Pathogenic
0
0
1
0
1
VUS
0
37
3
0
40
Likely Benign
0
0
0
3
3
Benign
0
1
0
0
1
Total03856397

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ELK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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